Levels of Biochemistry

R-S-RThioether

Lewis StructuresConsider outer shell valence electrons only

• H, Na, K have 1 electron

• Mg, Ca have 2 electrons

• B has 3 electrons

• C, Si have 4 electrons

• N, P have 5 electrons

• O, S, Se have 6 electrons

• Cl, I have 7 electrons

Na

Cl

Na+ + e-

+ e- Cl-

Na Cl

Na Cl

+

Cl

Cl

+Cl

Cl

N N N N

N NN N

+

Each atom has an octet

• Count the number of protons (+1)

• Count the unshared electrons (-1)

• Count the shared electrons (-0.5)

Assigning Formal Charges to Atoms

ClClProtons +7Unshared e- -6Shared e- -1Formal charge 0

H

C

H

O

Formal charge on oxygenProtons +6Unshared -4Shared -2Total 0

H3C

C

O

O

Formal charge on oxygenProtons +6Unshared -4Shared -2Total 0

Formal charge on oxygenProtons +6Unshared -6Shared -1Total -1

H3C NO2

C N

O

H

H

H

O

Formal charge on nitrogenProtons +5Unshared 0Shared -4Total +1

Oxidation States

• Electrons in a bond belong to the more electronegative atom

• For atoms that are equivalent then the electrons are split between them

Lewis structures tell you about reactivity

C C

O

H

H

H

O

C C

OH

H

H O

Resonance

C

C

C

C

C

CH H

H

H

H

H

CC

C

CC

C

H

H

HH

H

H

H

C

H

O

H

C

H

O+ -

Good Resonance Structuresmaximize covalent bondssurround 2nd and 3rd row atom with octetsminimize chargesplace negative charges on electronegative atoms

H

C C

O

HHH

H

C C

O

HHH

-

+

Moving electronsThe curved arrow formalism

O

H H

O

H

+ H+O

H

O

H H-

-

When drawing mechanisms:

Protons do not appear out of nowhere

Protons do not disappear into thin air

Double headed arrows indicate the movement of 2 electrons

Single headed arrows indicate the movement of 1 electron

Nucleophiles and electrophiles

• Nucleophile– An atom that bears a lone pair of

electrons– A resonance form that places a lone

pair on an atom– An atom that bears an acidic proton that

when it departs leaves behind a lone pair

Atom that bears a lone pair of electrons

+ H+O

H

-

Resonance structure that places a lone pair on an atom

H

O

C

CH

H

H

H

O

C

CH

H

H

+

-

Nucleophile

O

C

CH

H

H

H

Acidic proton that leaves and generates a lone pair

O

C

CH

H

H

-

Sometimes you need a very strong base to make the third type of nucleophile

H

C

H

H H

H

C

H

H

pKa = 45

No resonance

O

C

CH

H

H

H

O

C

CH

H

H

O

C

CH

H

H

Resonance

-

-

How to choose which nucleophile is better

O

C

H NH

H

Two nucleophiles

O

C

H NH

H

H+

O

C

H NH

H

H O

C

H NH

H

H

No resonance

+

+

O

C

H NH

H

H

+

Biologically important nucleophiles.

Nucleophiles and electrophiles

• Electrophile– An atom that bears a vacant orbital– A resonance form that generates a

vacant orbital– An atom that bears a leaving group that

when it departs generates a vacant orbital

Atoms with vacant orbitals

H

C

H

H+ Nu:-

Resonance structures that generate vacant orbitals

H

C

H

O

H

C

H

O+

-

Atoms that bear leaving groups that when they depart leave a vacant orbital

O

H H

O

HH+

-

+

electrophileLeaving group

• Electrophilicity ≠ positive charge

• Nucleophilicity ≠ negative charge

H3C

C

H3C

N+

CH3

CH3

H3C

C+

H3C

N

CH3

CH3

Biologically important electrophiles.

Chiral Molecules• Carbon atoms that have 4 distinct

substituents cannot be superimposed on their mirror image.

Molecules with more than one stereocenter

• Molecules that differ in only one stereocenter are stereoisomers

• Diastereomers are stereoisomers that have the same configuration at one stereocenter but different configurations at another

• Enantiomers have opposite configuration at all stereocenters

Chiral molecules are optically active: the different stereoisomers rotate the plane of polarized light in

opposite directions

• Dextrorotary: + rotation of the plane of light• Levorotary: - rotation of the plane of light

D-enantiomer

L-enantionmer

This does not tell us anything about the absolute configuration of a molecule.

Cahn-Ingold-PrelogSH > OH > NH2 > COOH > CHO > CH2OH > C6H5 > 2H > 1H

• Rank atoms directly attached to the chiral center and assign priorities based on decreasing atomic number• If a decision cannot be reached then move on to the second atom away from the chiral center• Multiple bonded atoms are considered an equivalent number of singly bonded atoms

CH

O = HC O

O

H2C OH

> CH

O

Therefore

Cahn-Ingold-Prelog

• Clockwise R

• Counterclockwise S

WATER: Molecule of the year…decade…century…millenium…

er…all time

Structure of ice.

Structures of the water trimer, tetramer, and pentamer.

Water is a rapidly fluctuating network of hydrogen bonding H2O molecules that reorder

every ~10-11 s

D = Dielectric Constant

• Ability to keep opposite charges apart• Generally increases with dipole moment

F =kq1q2

Dr2

F = forceq = chargek = constantr = distance

Dielectric Constants and Permanent Molecular Dipole Moments of Some

Common Solvents.

D for water is among the highesteven though the dipole is not the

strongest. Why?

D for water is among the highesteven though the dipole is not the

strongest. Why?

Water is highly ordered and resists thermal randomization that decreases the

dielectric constant

Solvation (hydration) of ions by oriented water molecules.

Hydrogen bonding by functional groups.

Hydrogen bonds are weak

• Van der Waals forces– 0.5-1.0 kcal mol-1

• O…H hydrogen bond– 1-3 kcal mol-1

• C-H covalent bond– 100 kcal mol-1

Associations of amphipathic molecules in aqueous solutions.

Ionic Mobilities in H2O at 25°C.

Mean lifetime of a hydronium ion is 10-12 s

This makes proton transfer reactions (acid base reactions) among the fastest in aqueous solutions.